免疫疗法被认为是一种有效的癌症治疗方法，引起了广泛的关注。然而，不充分的抗原性和免疫抑制的肿瘤微环境常常导致治疗效果不佳。在本研究中，我们开发了一种光活化反应性氧化物（ROS）放大系统（定义为"M-Cu-T"），通过触发肿瘤特异性免疫原性细胞凋亡诱导抗肿瘤免疫应答。在M-Cu-T中，利用M1巨噬细胞膜基质囊泡进行药物加载和肿瘤靶向治疗，使用光敏剂（meso-tetra(4-aminophenyl) porphyrin，TAPP）作为细胞凋亡诱导剂，铜离子（Cu2+）通过消耗细胞内抗氧化系统增强ROS引起的细胞凋亡。如预期的那样，制备的M-Cu-T能够富集于肿瘤细胞并产生ROS，进一步在激光激活下通过caspase 3介导的gasdermin E（GSDME）裂解诱导细胞凋亡。随之产生的免疫原性凋亡癌细胞分泌相关模式分子，诱导免疫原性细胞死亡，并激活用于免疫疗法的抗肿瘤免疫。在LLC和CT26癌症小鼠模型中观察到了有效的肿瘤消融。本研究为提高免疫原性并实现满意的治疗效果在癌症治疗中提供了启示。保留所有权利，本文受版权保护。

Immunotherapy is considered to be an effective treatment for cancer and has drawn extensive interest. Nevertheless, the insufficient antigenicity and immunosuppressive tumor microenvironment often cause unsatisfactory therapeutic efficacy. Herein, we develop a photo-activated reactive oxygen species (ROS) amplifying system (defined as "M-Cu-T") to induce anti-tumor immune response by triggering a tumor-specific immunogenic pyroptosis. In M-Cu-T, M1 macrophage membrane-based vesicles are used for drug loading and tumor targeting, photosensitizers (meso-tetra(4-aminophenyl) porphyrin, TAPP) are used as a pyroptosis inducer, copper ions (Cu2+ ) can enhance ROS-induced pyroptosis by consuming antioxidant systems in cells. As expected, the prepared M-Cu-T targets enrichment into tumor cells and cascades the generation of ROS, which further induces pyroptosis through caspase 3-mediated gasdermin E (GSDME) cleavage under laser activation. The pyroptotic cancer cells accompanyingly secrete related pattern molecules, induce immunogenic cell death, and activate anti-tumor immunity for immunotherapy. An effective tumor ablation is observed in LLC and CT26 cancer mouse model. This study provides inspiration for boosting the immunogenicity and achieving satisfactory therapeutic effect in cancer therapy. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.